tbuckley/cabot-search huggingface dataset:
Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial
Authors: Claudia M. Denkinger, Maike Janssen, Ulrike Schäkel, Julia Gall, Albrecht Leo, Patrick Stelmach, Stefan F. Weber, Johannes Krisam, Lukas Baumann, Jacek Stermann, Uta Merle, Markus A. Weigand, Christian Nusshag, Lars Bullinger, Jens-Florian Schrezenmeier, Martin Bornhäuser, Nael Alakel, Oliver Witzke, Timo Wolf, Maria J. G. T. Vehreschild, Stefan Schmiedel, Marylyn M. Addo, Felix Herth, Michael Kreuter, Phil-Robin Tepasse, Bernd Hertenstein, Mathias Hänel, Anke Morgner, Michael Kiehl, Olaf Hopfer, Mohammad-Amen Wattad, Carl C. Schimanski, Cihan Celik, Thorsten Pohle, Matthias Ruhe, Winfried V. Kern, Anita Schmitt, Hanns-Martin Lorenz, Margarida Souto-Carneiro, Mary Gaeddert, Niels Halama, Stefan Meuer, Hans-Georg Kräusslich, Barbara Müller, Paul Schnitzler, Sylvia Parthé, Ralf Bartenschlager, Martina Gronkowski, Jennifer Klemmer, Michael Schmitt, Peter Dreger, Katharina Kriegsmann, Richard F. Schlenk, Carsten Müller-Tidow
Journal: Nature Cancer (2022)

Abstract Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 ( n = 134) within four risk groups ((1) cancer ( n = 56); (2) immunosuppression ( n = 16); (3) laboratory-based risk factors ( n = 36); and (4) advanced age ( n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer ( P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.
Infection and transmission risks of COVID-19 in schools and their contribution to population infections in Germany: A retrospective observational study using nationwide and regional health and education agency notification data
Authors: Torben Heinsohn, Berit Lange, Patrizio Vanella, Isti Rodiah, Stephan Glöckner, Alexander Joachim, Dennis Becker, Tobias Brändle, Stefan Dhein, Stefan Ehehalt, Mira Fries, Annette Galante-Gottschalk, Stefanie Jehnichen, Sarah Kolkmann, Annelene Kossow, Martin Hellmich, Jörg Dötsch, Gérard Krause
Journal: PLoS Medicine (2022)

School-level infection control measures in Germany during the early Coronavirus Disease 2019 (COVID-19) pandemic differed across the 16 federal states and lacked a dependable evidence base, with available evidence limited to regional data restricted to short phases of the pandemic. This study aimed to assess the (a) infection risks in students and staff; (b) transmission risks and routes in schools; (c) effects of school-level infection control measures on school and population infection dynamics; and (d) contribution of contacts in schools to population cases.
Validation of a Deep Learning–Based Model to Predict Lung Cancer Risk Using Chest Radiographs and Electronic Medical Record Data
Authors: Vineet K. Raghu, Anika S. Walia, Aniket N. Zinzuwadia, Reece J. Goiffon, Jo-Anne O. Shepard, Hugo J. W. L. Aerts, Inga T. Lennes, Michael T. Lu
Journal: JAMA Network Open (2022)

Importance Lung cancer screening with chest computed tomography (CT) prevents lung cancer death; however, fewer than 5% of eligible Americans are screened. CXR-LC, an open-source deep learning tool that estimates lung cancer risk from existing chest radiograph images and commonly available electronic medical record (EMR) data, may enable automated identification of high-risk patients as a step toward improving lung cancer screening participation. Objective To validate CXR-LC using EMR data to identify individuals at high-risk for lung cancer to complement 2022 US Centers for Medicare &amp;amp;amp; Medicaid Services (CMS) lung cancer screening eligibility guidelines. Design, Setting, and Participants This prognostic study compared CXR-LC estimates with CMS screening guidelines using patient data from a large US hospital system. Included participants were persons who currently or formerly smoked cigarettes with an outpatient posterior-anterior chest radiograph between January 1, 2013, and December 31, 2014, with no history of lung cancer or screening CT. Data analysis was performed between May 2021 and June 2022. Exposures CXR-LC lung cancer screening eligibility (previously defined as having a 3.297% or greater 12-year risk) based on inputs (chest radiograph image, age, sex, and whether currently smoking) extracted from the EMR. Main Outcomes and Measures 6-year incident lung cancer. Results A total of 14 737 persons were included in the study population (mean [SD] age, 62.6 [6.8] years; 7154 [48.5%] male; 204 [1.4%] Asian, 1051 [7.3%] Black, 432 [2.9%] Hispanic, 12 330 [85.2%] White) with a 2.4% rate of incident lung cancer over 6 years (361 patients with cancer). CMS eligibility could be determined in 6277 patients (42.6%) using smoking pack-year and quit-date from the EMR. Patients eligible by both CXR-LC and 2022 CMS criteria had a high rate of lung cancer (83 of 974 patients [8.5%]), higher than those eligible by 2022 CMS criteria alone (5 of 177 patients [2.8%]; P &amp;amp;lt; .001). Patients eligible by CXR-LC but not 2022 CMS criteria also had a high 6-year incidence of lung cancer (121 of 3703 [3.3%]). In the 8460 cases (57.4%) where CMS eligibility was unknown, CXR-LC eligible patients had a 5-fold higher rate of lung cancer than ineligible (127 of 5177 [2.5%] vs 18 of 2283 [0.5%]; P &amp;amp;lt; .001). Similar results were found in subgroups, including female patients and Black persons. Conclusions and Relevance Using routine chest radiographs and other data automatically extracted from the EMR, CXR-LC identified high-risk individuals who may benefit from lung cancer screening CT.
Vertical integration of oncologists and cancer outcomes and costs in metastatic castration-resistant prostate cancer
Authors: Xin Hu, Joseph Lipscomb, Changchuan Jiang, Ilana Graetz
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background The share of oncology practices owned by hospitals (ie, vertically integrated) nearly doubled from 2007 to 2017. We examined how integration between hospitals and oncologists affected care quality, outcomes, and spending among metastatic castration-resistant prostate cancer (mCRPC) patients. Methods Using Surveillance, Epidemiology, and End Results–Medicare linked data and the Medicare Data on Provider Practice and Specialty, we identified Medicare beneficiaries who initiated systemic therapy for mCRPC between 2008 and 2017 (n = 9172). Primary outcomes included 1) bone-modifying agents (BMA) use, 2) time on systemic therapy, 3) survival, and 4) Medicare spending for the first 3 months following therapy initiation. We used a differences-in-differences approach to estimate the impact of vertical integration on outcomes, adjusting for patient and provider characteristics. Results The proportion of patients treated by integrated oncologists increased from 28% to 55% from 2008 to 2017. Vertical integration was associated with an 11.7 percentage point (95% confidence interval [CI] = 4.2 to 19.1) increased likelihood of BMA use. There were no satistically significant changes in time on systemic therapy, survival, or total per-patient Medicare spending. Further decomposition showed an increase in outpatient payment ($5190, 95% CI = $1451 to $8930) and decrease in professional service payment (−$4757, 95% CI = −$7644 to −$1870) but no statistically significant changes for other service types (eg, inpatient and prescription drugs). Conclusions Vertical integration was associated with statistically significant increased BMA use but not with other cancer outcomes among mCRPC patients. For oncologists who switched service billing from physician offices to outpatient departments, there was no statistically significant change in overall Medicare spending in the first 3 months of therapy initiation. Future studies should extend the investigation to other cancer types and patient outcomes.
Nirmatrelvir Use during the Omicron Surge
Authors: Ronen Arbel, Yael Wolff Sagy, Ariel Hammerman
Journal: New England Journal of Medicine (2022)

Nirmatrelvir Use during the Omicron SurgeTo the Editor: Arbel et al. (Sept. 1 issue) 1 found that among adults 65 years of age or older, the rates of hospitalization and death due to Covid-19 were lower among those who were treated with nirmatrelvir than among those who were not.We are uncertain whether these results are generalizable to the untreated population for two reasons.First, the vast majority of patients (96%) were not treated, which points to the presence of marked selection bias.The cause of this observation may be difficult to determine; however, it must be elucidated.The considerably skewed distribution of known confounders impairs extrapolation of the results to the untreated group.The use of propensity-score-based methods would allow for the probability of treatment in both groups to be matched, thereby enabling a more balanced, and perhaps stratified, comparison of outcomes between treated and untreated patients. 2Second, despite the fact that the authors corrected for known confounders, there were probably unmeasured confounders (e.g., severity of symptoms) that influenced the treatment decision through presumed treatment benefit.Although the results of the study are encouraging, differences between the groups and the absence of data on adverse events impair astute translation of the findings of this observational study to clinical practice and policy making.
DNA polymerase theta protects leukemia cells from metabolic-induced DNA damage
Authors: Umeshkumar Vekariya, Monika Maria Toma, Margaret Nieborowska-Skorska, Bac Viet Le, Marie-Christine Caron, Anna-Mariya Kukuyan, Katherine Sullivan-Reed, Paulina Podszywalow-Bartnicka, Kumaraswamy Naidu Chitrala, Jessica Atkins, Malgorzata Drzewiecka, Wanjuan Feng, Joe Chan, Srinivas Chatla, Konstantin Golovine, Jaroslav Jelinek, Tomasz Sliwinski, Jayashri Ghosh, Ksenia Matlawska-Wasowska, Gurushankar Chandramouly, Reza Nejati, Mariusz A Wasik, Stephen Sykes, Katarzyna Piwocka, Emir Hadzijusufovic, Peter Valent, Richard T Pomerantz, George Morton, Wayne Childers, Huaqing Zhao, Elisabeth Paietta, Ross L. Levine, Martin S. Tallman, Hugo Fernandez, Mark R Litzow, Gaorav Gupta, Jean-Yves Masson, Tomasz Skorski
Journal: Blood (2022)
An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia
Authors: Audrey Lasry, Bettina Nadorp, Maarten Fornerod, Deedra Nicolet, Huiyun Wu, Christopher J. Walker, Zhengxi Sun, Matthew T. Witkowski, Anastasia N. Tikhonova, Maria Guillamot-Ruano, Geraldine Cayanan, Anna Yeaton, Gabriel Robbins, Esther A. Obeng, Aristotelis Tsirigos, Richard M. Stone, John C. Byrd, Stanley Pounds, William L. Carroll, Tanja A. Gruber, Ann-Kathrin Eisfeld, Iannis Aifantis
Journal: Nature Cancer (2022)
DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression
Authors: Tim Kong, Angelo B. A. Laranjeira, Kangning Yang, Daniel A. C. Fisher, LaYow Yu, Laure Poittevin De La Frégonnière, Anthony Z. Wang, Marianna B. Ruzinova, Jared S. Fowles, Mary C. Fulbright, Maggie J. Cox, Hamza Celik, Grant A. Challen, Sidong Huang, Stephen T. Oh
Journal: Nature Cancer (2022)
Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia
Authors: Pirkka-Pekka Laurila, Martin Wohlwend, Tanes Imamura de Lima, Peiling Luan, Sébastien Herzig, Nadège Zanou, Barbara Crisol, Maroun Bou-Sleiman, Eleonora Porcu, Hector Gallart-Ayala, Michal K. Handzlik, Qi Wang, Suresh Jain, Davide D’Amico, Minna Salonen, Christian M. Metallo, Zoltan Kutalik, Thomas O. Eichmann, Nicolas Place, Julijana Ivanisevic, Jari Lahti, Johan G. Eriksson, Johan Auwerx
Journal: Nature Aging (2022)
Inhibition of MRTF activation as a clinically achievable anti-fibrotic mechanism for pirfenidone
Authors: Hsiao-Yen Ma, Jason A. Vander Heiden, Salil Uttarwar, Ying Xi, Elsa-Noah N'Diaye, Ryan LaCanna, Patrick Caplazi, Sarah Gierke, John Moffat, Paul J. Wolters, Ning Ding
Journal: European Respiratory Journal (2022)

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease characterised by aberrant fibroblast/myofibroblast accumulation and excessive collagen matrix deposition in the alveolar areas of lungs. As the first approved IPF medication, pirfenidone (PFD) significantly decelerates lung function decline while its underlying anti-fibrotic mechanism remains elusive.We performed transcriptomic and immunofluorescence analyses of primary human IPF tissues.We showed that myocardin-related transcription factor (MRTF) signalling is activated in myofibroblasts accumulated in IPF lungs. Furthermore, we showed that PFD inhibits MRTF activation in primary human lung fibroblasts at clinically achievable concentrations (half-maximal inhibitory concentration 50-150 µM, maximal inhibition >90%, maximal concentration of PFD in patients <100 µM). Mechanistically, PFD appears to exert its inhibitory effects by promoting the interaction between MRTF and actin indirectly. Finally, PFD-treated IPF lungs exhibit significantly less MRTF activation in fibroblast foci areas than naïve IPF lungs.Our results suggest MRTF signalling as a direct target for PFD and implicate that some of the anti-fibrotic effects of PFD may be due to MRTF inhibition in lung fibroblasts.
Moving towards patient-centred outcomes: the Severe Asthma Questionnaire
Authors: Drew Davies, Michael E. Hyland, Joseph W. Lanario, Rupert C. Jones, Matthew Masoli
Journal: European Respiratory Journal (2022)

<b>There is a need for more comprehensive measures of quality of life in severe asthma and the Severe Asthma Questionnaire provides a validated patient-centred core outcome measure for clinicians</b>https://bit.ly/3Bo936f
<i>Escherichia Coli:</i> What Is and Which Are<i>?</i>
Authors: Marta Cobo-Simón, Rowan Hart, Howard Ochman
Journal: Molecular Biology and Evolution (2022)

Escherichia coli have served as important model organisms for over a century-used to elucidate key aspects of genetics, evolution, molecular biology, and pathogenesis. However, defining which strains actually belong to this species is erratic and unstable due to shifts in the characters and criteria used to distinguish bacterial species. Additionally, many isolates designated as E. coli are genetically more closely related to strains of Shigella than to other E. coli, creating a situation in which the entire genus of Shigella and its four species are encompassed within the single species E. coli. We evaluated all complete genomes assigned to E. coli and its closest relatives according to the biological species concept (BSC), using evidence of reproductive isolation and gene flow (i.e., homologous recombination in the case of asexual bacteria) to ascertain species boundaries. The BSC establishes a uniform, consistent, and objective principle that allows species-level classification across all domains of life and does not rely on either phenotypic or genotypic similarity to a defined type-specimen for species membership. Analyzing a total of 1,887 sequenced genomes and comparing our results to other genome-based classification methods, we found few barriers to gene flow among the strains, clades, phylogroups, or species within E. coli and Shigella. Due to the utility in recognizing which strains constitute a true biological species, we designate genomes that form a genetic cohesive group as members of E. coliBIO.
High-Quality Genomes of Pangolins: Insights into the Molecular Basis of Scale Formation and Adaption to Myrmecophagous Diet
Authors: Dingyu Yan, Xier Luo, Jiabin Tang, Shanghua Xu, Kongwei Huang, Xiaobo Wang, Tong Feng, Tengcheng Que, Miaomiao Jia, Xiaobing Guo, Saif ur Rehman, Zhipeng Li, Yufeng Yang, Kaixiang Li, Kuiqing Cui, Jue Ruan, Qingyou Liu
Journal: Molecular Biology and Evolution (2022)

Pangolins are one of nature's most fascinating species being scales covered and myrmecophagous diet, yet relatively little is known about the molecular basis. Here, we combine the multi-omics, evolution, and fundamental proteins feature analysis of both Chinese and Malayan pangolins, highlighting the molecular mechanism of both myrmecophagous diet and scale formation, representing a fascinating evolutionary strategy to occupy the unique ecological niches. In contrast to conserved organization of epidermal differentiation complex, pangolin has undergone large scale variation and gene loss events causing expression pattern and function conversion that contribute to cornified epithelium structures on stomach to adapt myrmecophagous diet. Our assemblies also enable us to discover large copies number of high glycine-tyrosine keratin-associated proteins (HGT-KRTAPs). In addition, highly homogenized tandem array, amino content, and the specific expression pattern further validate the strong connection between the molecular mechanism of scale hardness and HGT-KRTAPs.
Association of Developmental Language Disorder With Comorbid Developmental Conditions Using Algorithmic Phenotyping
Authors: Rachana Nitin, Douglas M. Shaw, Daniel B. Rocha, Courtney E. Walters, Christopher F. Chabris, Stephen M. Camarata, Reyna L. Gordon, Jennifer E. Below
Journal: JAMA Network Open (2022)

Importance Developmental language disorder (DLD) is a common (with up to 7% prevalence) yet underdiagnosed childhood disorder whose underlying biological profile and comorbidities are not fully understood, especially at the population level. Objective To identify clinically relevant conditions that co-occur with DLD at the population level. Design, Setting, and Participants This case-control study used an electronic health record (EHR)–based population-level approach to compare the prevalence of comorbid health phenotypes between DLD cases and matched controls. These cases were identified using the Automated Phenotyping Tool for Identifying Developmental Language Disorder algorithm of the Vanderbilt University Medical Center EHR, and a phenome enrichment analysis was used to identify comorbidities. An independent sample was selected from the Geisinger Health System EHR to test the replication of the phenome enrichment using the same phenotyping and analysis pipeline. Data from the Vanderbilt EHR were accessed between March 2019 and October 2020, while data from the Geisinger EHR were accessed between January and March 2022. Main Outcomes and Measures Common and rare comorbidities of DLD at the population level were identified using EHRs and a phecode-based enrichment analysis. Results Comorbidity analysis was conducted for 5273 DLD cases (mean [SD] age, 16.8 [7.2] years; 3748 males [71.1%]) and 26 353 matched controls (mean [SD] age, 14.6 [5.5] years; 18 729 males [71.1%]). Relevant phenotypes associated with DLD were found, including learning disorder, delayed milestones, disorders of the acoustic nerve, conduct disorders, attention-deficit/hyperactivity disorder, lack of coordination, and other motor deficits. Several other health phenotypes not previously associated with DLD were identified, such as dermatitis, conjunctivitis, and weight and nutrition, representing a new window into the clinical complexity of DLD. Conclusions and Relevance This study found both rare and common comorbidities of DLD. Comorbidity profiles may be leveraged to identify risk of additional health challenges, beyond language impairment, among children with DLD.
Association of COVID-19 Vaccination Rates of Staff and COVID-19 Illness and Death Among Residents and Staff in US Nursing Homes
Authors: Soham Sinha, R. Tamara Konetzka
Journal: JAMA Network Open (2022)

It is important to understand the association between staff vaccination rates and adverse COVID-19 outcomes in nursing homes.To assess the extent to which staff vaccination was associated with preventing COVID-19 cases and deaths among residents and staff in nursing homes.This longitudinal cohort study used data on COVID-19 outcomes in Medicare- and Medicaid-certified nursing homes in the US between May 30, 2021, and January 30, 2022. Participants included the residents of 15 042 US nursing homes that reported COVID-19 data to the Centers for Disease Control and Prevention and passed Centers for Medicare & Medicaid Services data quality checks in the National Healthcare Safety Network.Weekly staff vaccination rates.Main outcomes are weekly COVID-19 cases and deaths among residents and weekly COVID-19 cases among staff. The treatment variable is the primary 2-dose staff vaccination rate in each facility each week.In the primary analysis of 15 042 nursing homes before the Omicron variant wave (May 30 to December 5, 2021) using fixed effects of facility and week, increasing weekly staff vaccination rates by 10 percentage points was associated with 0.13 (95% CI, -0.20 to -0.10) fewer weekly COVID-19 cases per 1000 residents, 0.02 (95% CI, -0.03 to -0.01) fewer weekly COVID-19 deaths per 1000 residents, and 0.03 (95% CI, -0.04 to -0.02) fewer weekly COVID-19 staff cases. In the secondary analysis of the Omicron wave (December 5, 2021, to January 30, 2022), increasing staff vaccination rates were not associated with lower rates of adverse COVID-19 outcomes in nursing homes.The findings of this cohort study suggest that before the Omicron variant wave, increasing staff vaccination rates was associated with lower incidence of COVID-19 cases and deaths among residents and staff in US nursing homes. However, as newer, more infectious and transmissible variants of the virus emerged, the original 2-dose regimen of the COVID-19 vaccine as recommended in December 2020 was no longer associated with lower rates of adverse COVID-19 outcomes in nursing homes. Policy makers may want to consider longer-term policy options to increase the uptake of booster doses among staff in nursing homes.